2-Hydroxy-3-methoxybenzoic acid attenuates mast cell-mediated allergic reaction in mice via modulation of the FcεRI signaling pathway

Abstract

Mast cells are important effector cells in immunoglobulin (Ig) E-mediated allergic reactions such as asthma, atopic dermatitis and rhinitis. Vanillic acid, a natural product, has shown anti-oxidant and anti-inflammatory activities. In the present study, we investigated the anti-allergic inflammatory effects of ortho-vanillic acid (2-hydroxy-3-methoxybenzoic acid, o-VA) that was a derivative of vanillic acid isolated from Amomum xanthioides. In mouse anaphylaxis models, oral administration of o-VA (2, 10, 50 mg/kg) dose-dependently attenuated ovalbumin-induced active systemic anaphylaxis and IgE-mediated cutaneous allergic reactions such as hypothermia, histamine release, IgE production and vasodilation; administration of o-VA also suppressed the mast cell degranulator compound 48/80-induced anaphylaxis. In cultured mast cell line RBL-2H3 and isolated rat peritoneal mast cells in vitro, pretreatment with o-VA (1-100 μmol/L) dose-dependently inhibited DNP-HSA-induced degranulation of mast cells by decreasing the intracellular free calcium level, and suppressed the expression of pro-inflammatory cytokines TNF-α and IL-4. Pretreatment of RBL-2H3 cells with o-VA suppressed DNP-HSA-induced phosphorylation of Lyn, Syk, Akt, and the nuclear translocation of nuclear factor-κB. In conclusion, o-VA suppresses the mast cell-mediated allergic inflammatory response by blocking the signaling pathways downstream of high affinity IgE receptor (FcεRI) on the surface of mast cells.

Gastroprotective Effect of Vanillin on Indomethacin-Induced Gastric Ulcer in Rats: Protective Pathways and Anti-Secretory Mechanism

“…Previous studies also noted vanillin's anti-inflammatory property [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Moreover it was proved that also vanillic acid regulated ulcerative colitis via inhibition NF-κB p65 activation and reduction in pro-inflammatory cytokines production; IL-1, IL-6 and TNF-α [33].…”

“…Also, vanillin produced a reduction in the histamine secreting mast cells in ethanol-induced peptic ulcer by reduction of mast cell degranulation [17]. Moreover, it was proved that vanillic acid, a metabolite oxidized product of vanillin, suppresses the mast cellmediated allergic inflammatory response by blocking the signaling pathways downstream of high affinity IgE receptor on the surface of mast cells [18]. Therefore, the gastroprotective effect of vanillin may be ascribed to the reduction of mast cell degranulation.…”

The Cell Research Trends of Asthma: A Stem Frequency Analysis of the Literature

“…Mechanism (mechan) and interventional effect were the two main directions of experimental research, but mechanism was more popular among scholars because stems about activation (activ) of cells or pathways [ 12 – 14 ], immune or cell response (respons) [ 15 – 17 ], genetic or protein expression (express) [ 18 – 20 ], and the role of cells or relevant genes or protein were always in the top 10 among all decades. The other 3 stems about mechanism research “product,” “induc,” and “mediat” were mainly frequent in “production of cytokines” [ 21 ], “protein or allergen-induced” [ 22 ], and “cell-mediated” [ 23 ], respectively. Inhibition was a typical intervention effect and its stem “inhibit” was ranked in our results.…”

SG-SP1 Suppresses Mast Cell-Mediated Allergic Inflammation via Inhibition of FcεRI Signaling

“…FcεRI is a heterotetrameric receptor comprised of an IgE-binding α subunit, the membrane tetraspanning β subunit, and two identical disulphide linked γ subunits (4). Assembly of the heterotetrameric structure of FcεRI is initiated by the phosphorylation of the immunoreceptor tyrosine-based activating motifs on the β and γ subunits by Src family kinases such as Lyn and Fyn (8,9). Lyn and Syk phosphorylate several adaptor molecules and enzymes to regulate mast cell activation.…”